Article Archive
November/December 2018

Memory Loss and Medication
By Lindsey Getz
Today's Geriatric Medicine
Vol. 11 No. 6 P. 20

Research raises new concerns about an association between anticholinergic drugs and dementia.

Research shows that 50 million people worldwide are living with dementia. According to Alzheimer's Disease International, that means someone in the world develops dementia every three seconds. It's believed that this number will soar to as high as 131.5 million people by 2050.

The causes of dementia vary. While Alzheimer's disease is thought to account for between 60% to 80% of dementia cases, it's not the only cause, and research efforts have long been underway to better understand memory loss and what might be done to prevent it.

As a result of some of these studies, a connection between medications and increased risk of memory loss has emerged. Recent research linking a frequently prescribed group of drugs to an increased risk of dementia has researchers convinced that prevention may be more in the hands of clinicians than was previously believed. There's no question that many older adults or their loved ones likely are concerned about their risk of memory loss. That there may be some controllable factors affecting their likelihood of developing it is important news for this patient population.

An international team of investigators from the United States, the United Kingdom, and Ireland analyzed more than 27 million prescriptions as recorded in the medical records of 40,770 patients older than 65 diagnosed with dementia and compared them with the records of 283,933 older adults without dementia. They found greater incidence of dementia among patients who were prescribed anticholinergic drugs. More specifically, they found that people who for a year or more used certain types of anticholinergics, specifically those used to treat depression, Parkinson's, and urinary incontinence, had about a 30% increased risk of developing dementia.

This raises red flags that geriatrics professionals should be aware of, as many of their patients are likely to be using these medications.

Anticholinergic Drugs
Anticholinergic drugs work by blocking a specific neurotransmitter called acetylcholine in the central and peripheral nervous systems. While it's unclear exactly why these medications increase dementia risk, one theory is that some may block the normal activity of acetylcholine in the regions of the brain associated with memory loss and cognition. Since levels of acetylcholine are known to be significantly lower in patients with Alzheimer's disease, this potential blockage could result in memory loss.

Drugs with anticholinergic activity fall across a fairly broad spectrum, and the research indicated that certain anticholinergic drugs posed more risk than others.

A Credible Link
The largest and most detailed study of the long-term impact of anticholinergic drugs, "Anticholinergic Medication and Risk of Dementia: Case-control Study," published in BMJ earlier this year, is also the first to look at different classes of anticholinergic medications instead of the category as a whole.

While the research didn't find a link between dementia and use of anticholinergic drugs such as antihistamines or those used for abdominal cramps, long-term use of certain anticholinergic drugs, including antidepressants such as Paxil and Elavil, medications for bipolar disorder including Zyprexa and Seroquel, and drugs used for bladder conditions and Parkinson's disease, increased dementia risk. Most notably, according to study coauthor Malaz Boustani, MD, MPH, a Regenstrief Institute and Indiana University Center for Aging Research investigator, the risk was greater even when the medications had been taken 20 years before the diagnosis of cognitive impairment.

Mindful Medicine
"The take-home message from these findings is that clinicians working with older adults must master the deprescribing message and stop these medications as soon as safely possible," says Boustani, who's also the founder of the Indiana Clinical and Translational Science Institute's Indiana University Center for Health Innovation and Implementation Science and the chief innovation and implementation officer for Sandra Eskenazi Center for Brain Care Innovation. "Physicians should review all of the anticholinergic medications, including over-the-counter drugs, that patients are taking and determine safe ways to take them off of these medications in order to preserve brain health."

Of course, older adults should not cease any medication without first discussing these changes with a health care provider. It's important to note that while this study has found a link between anticholinergic drugs and dementia, that's not to say that anticholinergic drugs cause dementia. The study did not investigate the cause behind the link. Even so, Shelly Gray, PharmD, MS, a professor in the department of pharmacy and director of the Plein Center for Geriatric Pharmacy Research at the University of Washington School of Pharmacy, says it's imperative providers familiarize themselves with the research.

"This is a well-conducted study and also the second of its kind, meaning the evidence is building," Gray says. "A previous study found a similar association between anticholinergic drugs and dementia. Therefore, the fact that this is not only such an extensive study, but also not the first of its kind, would indicate that providers should take the findings seriously. It would be my recommendation that providers should avoid using anticholinergic medications, when possible, that are associated with risks."

Providers and their patients, she adds, must have meaningful conversations about steps that can be taken to cease these medications without having a detrimental impact on patients. "For most conditions, there are safe alternatives to anticholinergic drugs that do not pose so much risk—including some nondrug measures when indicated," Gray says. "However, in situations where providers feel they must use an anticholinergic drug and the benefits truly outweigh the risks, then I would advise the lowest effective dose and close monitoring. If the prescribing provider monitors the treatment closely and feels it's not highly effective, I would argue it's not worth the associated risks."

Gray adds that a "bigger picture point" is that for many years it's been advised to be careful prescribing anticholinergic drugs to older adults due to other adverse effects including constipation, blurry vision, and increased fall risk. "The studies being published about dementia risk are really just adding to an already long list of adverse effects that are associated with these types of medications," she says. "It seems that this is yet another reason to avoid taking these drugs whenever possible."

Anticholinergic medications are not the only drugs associated with memory loss. Even where research hasn't confirmed a link, there's substantial anecdotal evidence that some may be linked to impairment, says Armon B. Neel, Jr, PharmD, a geriatric pharmacist who has counseled and educated patients and their caregivers on the safe and effective use of medication for more than 40 years.

Other drugs that may impair thinking abilities in older adults include opiates, antipsychotics, and mood stabilizers. While in some instances it's challenging, elder care clinicians should do their best to look for alternatives whenever there are risks or it seems the patients aren't functioning their best, Neel says. In addition, he advises, look carefully at dosing and consider whether the patient may be receiving more medication than is necessary.

Work Closely With Patients
Because patients may be daunted by the prospect of discontinuing a drug they've been taking for many years, Boustani urges clinicians to work closely with patients who are discontinuing use of anticholinergic drugs because they've been linked to dementia.

"It's incredibly important that clinicians who are working with older adults provide assurance that they are going to monitor the patient's response to the cessation of a drug," he says. "Patients do not want to feel as though they're just on their own to deal with this. Clinicians need to assure patients that upon return of any symptoms, they're are going to try an alternative treatment."

Boustani adds that working closely with patients also provides an opportunity to increase their awareness of their personal dementia risk. The vast majority of older adult patients, he says, likely are unaware of the link between anticholinergic drugs and dementia. Boustani's unpublished research proves this. In a recent study, the researchers interviewed 24 older adults taking anticholinergic medications and asked them about the drugs' link to dementia. None of the study participants was aware of the connection. However, once made aware, roughly 90% of participants wanted to speak to their doctor about changes to their regimens.

"Patients have the right to be made aware of the potential risks of any medications they're taking, but more often than not, this information is breezed over," Boustani adds. Clinicians, he says, have a responsibility to spend more time educating patients.

Generally, overmedication of older adults is a serious concern, says Neel, author of Are Your Prescriptions Killing You?: How to Prevent Dangerous Interactions, Avoid Deadly Side Effects, and Be Healthier With Fewer Drugs. But with the increasing knowledge of the link between anticholinergic drugs and dementia risk, there's more cause for alarm.

However, one of the obstacles to action is the fact that many older adult patients fail to bring up the over-the-counter drugs they're taking. "It's not uncommon for older adults to be taking five or six over-the-counter drugs that they fail to mention," Neel says. "It's important that the provider really presses on the issue of a complete list of medications."

Gray agrees. "It's imperative that older adults inform their health care providers of all over-the-counter medications they are taking so that providers can be aware of the use of any anticholinergic drugs—the goal being to keep the usage to a minimum," she says.

Because medications with anticholinergic properties are available without a prescription, it's quite possible that older adults may not be aware they're taking a medication that falls into this category, Gray adds. It's important for providers to stress that questions pertaining to medications refer to both prescription and over-the-counter medications. "People may not give a lot of thought to the risks associated with over-the-counter medications such as a sleep aid," she says.

Improvements in Care for Older Adults
Improvements in geriatric medicine are needed, says Neel, who observes that a lack of understanding of geriatric care can exacerbate medication problems. "This is a big problem that needs to be addressed," he continues. "When an older patient has a medical problem, the immediate inclination is to prescribe a medication and send them on their way. Then their memory starts to decline, and instead of looking at it being a side effect of the drug, the provider just overlooks it as something that's age related. Prescribers need to pay detailed attention to what they're prescribing and how it's impacting the patient. Sometimes it's a case of too much, when only a little was needed."

Overmedication, Neel says, also may occur when there's more emphasis on treating symptoms than on finding the root cause of a medical concern.

"It's quite common for older adults to be on a number of different medications for a number of different issues," Neel says. "But how many of those issues were caused by a medication? You see this all of the time—a symptom arises that's a result of a medication, and instead of taking the patient off of that medicine, doctors add another one to treat the new symptom. It just continues to compound. Whether it's anticholinergic drugs or something else, it's an issue that needs to be addressed."

Hope on the Horizon
While the reported link between anticholinergic medications and dementia rightfully has some concerned, it's also information being welcomed by many who are hopeful that increased understanding of memory loss can help prevent it in the future.

According to Boustani, this is exciting news for many who thought symptoms of memory loss were inevitable among certain patient populations. "The important news to come out of this is the fact that this is a modifiable risk factor," he says.

In addition to medication risks, it's also important to note and address the other modifiable risk factors that have already been identified. For example, physical inactivity, social isolation, and smoking are associated with an approximate 25% to 50% higher risk of dementia.

"Patients have the right to know that changes they make can have an impact on their brain health," Boustani says.

— Lindsey Getz is an award-winning freelance writer based in Royersford, Pennsylvania.